Spatial propagation of interictal discharges along the cortex

Abstract

Interictal discharges (IIDs) accompany epileptic seizures and highlight the mechanisms of pathological activity. The propagation of IIDs along the neural tissue is not well understood. To simulate IID propagation, this study proposes a new mathematical model that uses the conductance-based refractory density approach for glutamatergic and GABAergic neuronal populations. The mathematical model is found to be consistent with experimental double-patch registrations in the 4-aminopyridine in vitro model of epilepsy. In slices, the spontaneous activity of interneurons leads to their synchronization by means of the depolarizing GABAmediated response, thus initiating IIDs. Modeling reveals a clustering of interneuronal synchronization followed by IIDs with activity fronts that propagate along the cortex. The GABA-mediated depolarization either remains to be subthreshold for the principal neurons and thus results in pure GABAergic IIDs (IID1s) or leads to glutamatergic excitation, thus resulting in another type of IIDs (IID2s). In both the model and experiment, IIDs propagate as waves, with constant activity profiles and velocity. The speed of IIDs is of the order of tens of mm/s and is larger for IID2s than for IID1s (40 and 20 mm/s, respectively). The simulations, consistent with experimental observations, show that the wavelike propagation of IIDs initiated by interneurons is determined by local synaptic connectivity under the conditions of depolarizing GABA.

Keywords: Conductance-based refractory density model; Double patch-clamp; Epilepsy; GABA; Interictal discharges; Mathematical modeling.